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Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion.
J Pharm Sci. 1992 Mar; 81(3):221-5.JP

Abstract

The influences of absorption rate and dosage size on the pharmacokinetics of ibuprofen (IB) enantiomers were studied in six healthy subjects. Rapidly absorbed solutions (50, 100, 200, 400, 600, and 1200 mg) and regular 600-mg tablets of racemic IB were given orally, and plasma concentration-time courses of the enantiomers were followed. Solutions were absorbed faster (tmax less than 0.25 h) than the tablet (tmax = 2.17 +/- 1.17 h). While the S:R AUC ratios were unaffected by increasing the dose, they were significantly greater after the tablet (1.35 +/- 0.14) as compared with the solutions (1.15 +/- 0.16 to 1.24 +/- 0.26). This indicates a greater extent of chiral inversion for the tablet, perhaps due to a longer residence time in the gut, thereby allowing more presystemic inversion. To test this hypothesis, R-IB was incubated at 37 degrees C in the presence of excised segments of human ileum and colon obtained from three patients. Chiral inversion was evident in all segments. After 3 h, the extent of inversion ranged from 20.0 to 33.0%. In addition, incubation resulted in the formation of up to 23.3 and 13.0% of acylglucuronides of S- and R-IB, respectively. In all subjects, the AUC-dose relationships were nonlinear, indicating a gradual increase in the clearance of both enantiomers due, perhaps, to a parallel saturation of plasma protein binding sites. In humans, the chiral inversion of IB is not influenced by the dosage size but is enhanced by prolongation of the residence time in the intestine.

Authors+Show Affiliations

Faculty of Pharmacy, University of Alberta, Edmonton, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1640357

Citation

Jamali, F, et al. "Human Pharmacokinetics of Ibuprofen Enantiomers Following Different Doses and Formulations: Intestinal Chiral Inversion." Journal of Pharmaceutical Sciences, vol. 81, no. 3, 1992, pp. 221-5.
Jamali F, Mehvar R, Russell AS, et al. Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion. J Pharm Sci. 1992;81(3):221-5.
Jamali, F., Mehvar, R., Russell, A. S., Sattari, S., Yakimets, W. W., & Koo, J. (1992). Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion. Journal of Pharmaceutical Sciences, 81(3), 221-5.
Jamali F, et al. Human Pharmacokinetics of Ibuprofen Enantiomers Following Different Doses and Formulations: Intestinal Chiral Inversion. J Pharm Sci. 1992;81(3):221-5. PubMed PMID: 1640357.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion. AU - Jamali,F, AU - Mehvar,R, AU - Russell,A S, AU - Sattari,S, AU - Yakimets,W W, AU - Koo,J, PY - 1992/3/1/pubmed PY - 1992/3/1/medline PY - 1992/3/1/entrez SP - 221 EP - 5 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 81 IS - 3 N2 - The influences of absorption rate and dosage size on the pharmacokinetics of ibuprofen (IB) enantiomers were studied in six healthy subjects. Rapidly absorbed solutions (50, 100, 200, 400, 600, and 1200 mg) and regular 600-mg tablets of racemic IB were given orally, and plasma concentration-time courses of the enantiomers were followed. Solutions were absorbed faster (tmax less than 0.25 h) than the tablet (tmax = 2.17 +/- 1.17 h). While the S:R AUC ratios were unaffected by increasing the dose, they were significantly greater after the tablet (1.35 +/- 0.14) as compared with the solutions (1.15 +/- 0.16 to 1.24 +/- 0.26). This indicates a greater extent of chiral inversion for the tablet, perhaps due to a longer residence time in the gut, thereby allowing more presystemic inversion. To test this hypothesis, R-IB was incubated at 37 degrees C in the presence of excised segments of human ileum and colon obtained from three patients. Chiral inversion was evident in all segments. After 3 h, the extent of inversion ranged from 20.0 to 33.0%. In addition, incubation resulted in the formation of up to 23.3 and 13.0% of acylglucuronides of S- and R-IB, respectively. In all subjects, the AUC-dose relationships were nonlinear, indicating a gradual increase in the clearance of both enantiomers due, perhaps, to a parallel saturation of plasma protein binding sites. In humans, the chiral inversion of IB is not influenced by the dosage size but is enhanced by prolongation of the residence time in the intestine. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/1640357/Human_pharmacokinetics_of_ibuprofen_enantiomers_following_different_doses_and_formulations:_intestinal_chiral_inversion_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)48767-2 DB - PRIME DP - Unbound Medicine ER -